Group BStreptococcusInduces a Robust IFN-γResponse by CD4⁺T Cells in anIn VitroandIn VivoModel

Abstract

Group B Streptococcus (GBS) serotype III causes life-threatening infections. Cytokines have emerged as important players for the control of disease, particularly IFN-γ. Although potential sources of this cytokine have been proposed, no specific cell line has ever been described as a leading contributor. In this study, CD4+ T cell activation profiles in response to GBS were evaluated through in vivo, ex vivo, and in vitro approaches. Total splenocytes readily produce a type 1 proinflammatory response by releasing IFN-γ, TNF-α, and IL-6 and actively recruit T cells via chemokines like CXCL9, CXCL10, and CCL3. Responding CD4+ T cells differentiate into Th1 cells producing large amounts of IFN-γ, TNF-α, and IL-2. In vitro studies using dendritic cell and CD4+ T cell cocultures infected with wild-type GBS or a nonencapsulated mutant suggested that GBS capsular polysaccharide, one of the major bacterial virulence factors, differentially modulates surface expression of CD69 and IFN-γ production. Overall, CD4+ T cells are important producers of IFN-γ and might thus influence the course of GBS infection through the expression balance of this cytokine.

Immune-responsiveness of CD4+ T cells during Streptococcus suis serotype 2 infection

“…In the case of S. suis , only low expression of CD69 was observed on CD4 + T cells activated in vitro . This is in contrast to GBS and S. pneumoniae which induce a significant up-regulation of CD69 on T cells during the infection1929. S. suis also failed to induce significant levels of surface expression of CD40L, an important co-stimulatory molecule involved in T cell activation.…”

“…Furthermore, GBS and S. suis are the sole Gram-positive bacteria harbouring terminal sialic acid in their CPSs. However, despite these similarities, the production of TNF-α, IFN-γ, IL-6, IL-10, CCL3, and CXCL9 was much lower in the spleen of S. suis -infected mice than it was in GBS-infected mice under the same experimental conditions19.…”

“…Limited development of a memory response was further supported by the lack of expansion of the effector memory and central memory CD4 + T cell subsets in the spleen of S. suis- infected mice, even after a boost infection. In contrast, GBS-infected mice have been reported to display enhanced % of central memory CD4 + T cells following a boost-infection under the same experimental conditions19.…”

“…The highest dose was selected for these studies to achieve optimal antigenic stimulation at a short post-infection time in order to capture the early events of antigen presentation and immune cell activation within the spleen environment. After red blood cell lysis and washing, total splenocytes were plated at a concentration of 5 × 10 6 cells/ml in RPMI complete medium (without antibiotics) in 24-well flat bottom plates, and incubated for 48 h. However, after the initial 6 h of ex vivo incubation, gentamycin was added to the culture to control the bacterial load and prevent cell toxicity as reported previously19. Total splenocytes from control (placebo) animals were similarly treated.…”

“…5a. Analysis of IL-7Rα expression was used to further identify memory cells (CD44 high IL-7Rα + ) within these two subsets as previously described19.…”